I propose to study some of the basic phenomena of the immune response, that is the processes of recognition of antigens and of initiation of the stimulation for cell differentiation. The research proposal continues our efforts of the past years of trying to characterize receptors for antigen on the surfaces of lymphocytes and macrophages. The present proposal covers 3 interrelated subjects. First it attempts to characterize cytochemically the Ig receptor on B lymphocytes and the handling of antigen by specifically committed cells. We would like to determine how the Ig molecules are assembled on the surface and the factors that control the distribution and turnover of this receptor. The manner in which the B cell receptor interacts with antigenic moieties is probably a fundamental step in cell stimulation. We propose to use hapten attached covalently to a variety of carrier proteins in such a way as to have a variety of conjugates varying in their distribution and density of the haptenic determinant. The handling of these conjugates by the B lymphocyte will be studied by a series of functional and sophisticated morphological approaches. The relationship between surface handling of antigens and cell triggering is one area that the proposal explores thoroughly using in vitro methods for antibody formation. A second subject concerns the nature of the antigen receptor of the T lymphocyte and here we will attempt further cytochemical analysis plus attempts to purify antigen-committed T cells and to isolate chemically their receptors. Finally we are keen on continuing our past studies on the immunogenic role of macrophages and this time we propose to examine macrophages from strains of mice that have genetic differences in immune responsiveness. We also plan to study the pathways by which lymphocytes active macrophages (for increased bactericidal activity, for example) using mainly in vitro culture assays.